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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5637_Библиотеки_им_академика_М_И_Перельмана
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100 A. Das and J. Kumar
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Optimization of Tablet Coating
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Preksha Vinchhi and Mayur M. Patel
Abbreviations
API Active pharmaceutical ingredient
CFD Computational fluid dynamics
CMAs Critical material attributes
CMH Cubic metres per hour
CPPs Critical processing parameters
CQAs Critical quality attributes
DEM Discrete element modelling
DOE Design of experiment
GPU Graphical processor unit
HPMC Hydroxy propyl methylcellulose
NIR Near-infrared spectroscopy
PAT Process analytical technology
PQRI Product quality research institute
QBD Quality by design
QTPP Quality target product profile
1 Introduction
1.1 History
Since many centuries, the coating of pharmaceutical formulations has been practised. Late back in the ninth to eleventh century A.D., the first reports related to this
topic were affirmed. In the famous book Al Qanun, the author ‘Avicenna’ reported
P. Vinchhi · M. M. Patel ()
Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad, India
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2022
A. Fytopoulos et al. (eds.), Optimization of Pharmaceutical Processes, Springer
Optimization and Its Applications 189, https://doi.org/10.1007/978-3-030-90924-6_5
103
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coating of pills using silver. Earlier, amongst various solid dosage forms, pills
were the primary solid dosage form widely used. Diverse materials were employed
to coat the pills, for instance, sugar, honey, talc, gelatin, silver, gold, etc. The
primary purpose of pill coating in those days was to mask the unpleasant odour
and taste of active pharmaceutical ingredients (APIs). Initially, the coating process
was conducted in copper pans hanging by two chains above the fire. In 1840, the first
hand-operated coating pan was represented, and in 1844 a patent for the spherical
pan was approved [1]. In the nineteenth century, the modern pharmaceutical coating
began with sugar coating with the main purpose of increasing the palatability
of bitter medicines. However, the sugar coating requires longer processing time,
requires a high level of operator expertise, has a possibility of microbial growth in a
sugar solution, and has a lack of automation in the process. Thus, alternative coating
methods were developed to overcome issues pertaining to sugar-coated tablets. In
1930, noteworthy efforts in tablet coating were done in which polymer films were
proposed as an option for substrate coating. Thereafter, in 1954, the first film-coated
tablets were introduced into the market by Abbott Laboratories. The film-coated
tablets were preferred more than sugar-coated owing to the benefit of a less complex
manufacturing process requiring lesser time, cost and labour.
1.2 Definition and Scope
Coating is a widely employed unit operation involved in the manufacturing of solid
dosage forms. The procedure by which a solid dry film of coating composition gets
smeared over the exterior of desired dosage forms (tablets, pellets or granules) is
referred to as coating. The coating composition may involve plasticizer, flavouring
and colouring material, polyhydric alcohol, wax, fillers, sugar, resins and gums.
In modern pharmaceutical coating, polymers and polysaccharides are principal
coaters along with plasticizers and pigments. During the coating process, several
precautions should be considered, as coating should be unwavering and sturdy.
Avoiding the use of organic solvents is also preferred by ICH guidelines to improve
the product safety profile. Film coating (aqueous and non-aqueous) and sugar
coating are the two main categories of tablet coating. The tablets that are prone
to moisture degradation or oxidation are film-coated in order to increase their shelf
life and make them more swallowable by imparting them a smooth finish. Although
the step of coating adds up cost and time to the manufacturing of solid dosage forms,
it is still highly favoured as it bestows numerous advantages.
1.3 Significance of Coating
Tablet coating is usually intended to mask unpleasant odour or taste, produce an
elegant product, increase stability against moisture and light or modify drug release
profiles. The drug’s shelf life increases by coating as protection from environmental
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effects such as humidity, light, oxygen, etc. is achieved. Also, the coating acts as
an important aspect for high-speed packaging as it reduces the friction between
tablets and packaging material. The dust generation from the tablets also reduces
due to coating that helps to protect the workers against exposure to harmful drugs
while tablet processing. The identification of the tablets also gets easier for the
patients as well as healthcare providers due to coating. Tablet coating allows the
marketed producta brand identity as wellas enhances its aesthetic appeal.A suitable
surface for printing is created by coating. Tablet coating is an extensively employed
strategy that is regularly selected to control the dissolution rate of the drug in the
gastrointestinal tract. The site-specific drug release in the body can also be achieved
by coating, for example, enteric coating facilitates drugrelease in the intestine. Also,
the drug release rate can be controlled by coating, for instance, sustained or delayed
drug release. Sequential drug release can also be achieved by coating [2].
1.4 Optimization of Tablet Coating
The recent regulatory initiatives outlined in various guidelines, such as ICHQ8,
ICHQ9 and ICHQ10, require the science and risk-based manufacturing of product
and processes built on ‘quality by design’ (QBD) principles and process analytical
technologies (PAT). The application of QBD approaches is done to enhance
the knowledge of product performance influenced by the manufacturing process
technique, processing parameters and material attributes. The foremost step for optimizing the coated product is by employing QBD principles in establishing quality
target product profile (QTPP) for both the core tablet and coated tablet. Thereafter,
the determination of critical quality attributes (CQAs) of both core tablet and coated
tablet is done. Furthermore, the critical processing parameters (CPPs) and critical
material attributes (CMAs) are identified by risk assessment. Implementation of
design of experiments (DOEs) is done to establish the design space of CPPs for
the tablet coating procedure. The risk assessment is done on the basis of basic
principles, historic knowledge and the data generated from initial experiments. After
establishing sufficient understanding of the coating process, identification of design
space for CPPs can be conducted by establishing small DOEs for optimizing the
process. After optimizing the coating process by applying appropriate modelling
strategies and data analysis, the generated information helps to enable real-time
processing decisions and processing controls by employing PAT tools for ensuring
the manufacturing of consistent product quality. The chapter provides information
regarding various tablet coating techniques commonly employed in pharmaceutical
industries, types of equipment used in tablet coating, the impact of various material
and processing attributes on those techniques, novel tablet coating techniques and
PAT tools employed for tablet coating optimization.
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2 Tablet Coating Techniques
2.1 Sugar Coating
Originally, tablet coating was developed to mask the bitter taste using sugar and
to offer an alluring appearance at the core. Despite increased interest in film
coating since 1950, the pharmaceutical technique of sugar coating has been widely
performed. Various advantages of sugar coating technique are as follows, (a) It is
a simplified technique, (b) It is an extensively accepted technique, (c) It involves
use of inexpensive and readily available material, (d) Reworking processes are
feasible. The steps involved in sugar-coating technique are explained in Table 1.
Though sugar coating provides an elegant and aesthetically delighting coat of even
colouration and high gloss, the process also has some drawbacks. The technique
is lengthy and also requires proper operator skills. The increase in tablet weight
is at least 30–50% which leads to a significant increase in tablet size. Also,
on sugar-coated tablets, intangliations cannot be made; thus, there is a need to
Table 1 Steps involved in sugar coating
Steps involved Description
1. Seal coating As sugar coating permits water to directly penetrate into the substrate
2. Subcoating It offers curving of tablet edges and also increases the tablet weight. The
3. Syrup coating This step is also known as smoothing or grossing. For formulating a
4. Colour coating Colour coating is an imperative step as it has a significant visual impact.
5. Polishing To achieve glossy, smoothly finished tablets, this step is done. Various
which can affect the product stability and also lead to early tablet
disintegration. The aim of seal coating is to provide preliminary protection
to the substrate and avert the movement of ingredients of the substrate to
the coating layer. Water-resistant material such as zein, cellulose acetate
phthalate, polyvinyl acetate phthalate and pharmaceutical shellac is
sprayed in alcoholic form to obtain waterproof coat
subcoating formulation comprises of high quantity of fillers like talc,
calcium carbonate, titanium dioxide and kaolin. For improving the
structural integrity, the auxiliary film formers like gelatin, acacia and
cellulose derivatives can also be incorporated. A rise in weight up to
50–100% occurs after this step. Typically, two key approaches for
performing subcoating are suspension subcoating method and lamination
method
good-quality sugar-coated product, it is essential to make the surface of
the substrate smooth before colour coating. To conceal the irregularities
on the tablet surface, this step is performed by applying 70% sucrose
syrup comprising of titanium dioxide as a whitening agent or opacifier
The desired colour is obtained by adding various colourants either by
dissolving them in coating syrup (water-soluble dye) or by dispersing
them in coating syrup (water-insoluble pigments)
types of polishing systems involve alcoholic slurries wax, waxes in
organic solution and dry waxes in a powdered state. It is essential to polish
the sugar-coated tablets as they are dull when formulated
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print identification marks or logos. Moreover, longer coating time, difficulty in
automation and troubles in process standardization have led to the development of
improved coating technique [3].
2.2 Film Coating
As sugar-coating technique is very lengthy and dependent on coating operator
skills, it is being replaced by film coating technique. Currently, it is the most
extensively employed coating method. It allows engraving of logos or any other
type of identification on the core of the tablet with intangliations staying readable
after coating. Also, the weight gain after the film coating is much lesser compared
to sugar coating. For the preparation of controlled release products, the film coating
technique is substantially faster and easily adaptable. The film coating process
includes spraying of a solution comprising of polymer, plasticizer and pigments on a
rotating tablet bed which leads to the formation of a uniform, thin film on the surface
of the tablet. The atomized liquid impinges on the substrate’s surface, and the film
formation takes place as the solvent evaporates. The mechanism of film formation
on a substrate is represented in Fig. 1. However, with aqueous dispersions, the film
formation is difficult as the polymer spheres dispersed on the substrate must also
coalesce. In such cases, to promote the film formation and polymer coalescence,
the substrate is stored at elevated temperatures post coating. The duration required
for the formation of a proper coalesced film is dependent on numerous variables
involving the processing conditions as well as formulation variables [4]. The ideal
material for film coating should have the characteristics such as the following: (a) It
should produce an elegant coat; (b) it should remain stable in the presence of light,
moisture or heat; (c) it must have good solubility in the desired solvent; (d) it must
be pharmacologically inert and non-toxic; (e) it should not produce disagreeable
taste, odour or colour; and (f) it should be compatible with other coating additives.
The polymer selection depends on the desired drug release rate or desired drug
release site, i.e. stomach or intestine. Hydroxypropyl methylcellulose (HPMC),
povidone, ethylcellulose, methyl hydroxyethylcellulose, etc. are examples of widely
used coating polymers. HPMC phthalate, cellulose acetate phthalate and acrylate
polymers (Eudragit S and Eudragit L) are the widely employed enteric coating
polymers [5].
Types of Film Coating
The film coating can be categorized into two types, viz. organic film coating and
aqueous film coating. When the polymer utilized for coating is water-insoluble,
usually organic solvent is used to prepare the coating solution. A mixture of waterinsoluble polymers, pigments and excipients is solubilized in an organic solvent and
then sprayed on the substrate and subsequently dried by providing heat to form a
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Fig. 1 Schematic representation of film formation mechanism
film on the substrate. Majority of the polymers are soluble in organic solvents so
they provide a wide range of polymer alternatives for organic film coating. Employing organic solvents for the coating process reduces the hydrolytic degradation of
drug moiety. Also, the use of hydrophobic polymers is advantageous as they provide
moisture-protective coating and in turn reduce the water vapour permeability of
film. Thus, for moisture-sensitive drug moieties, organic film coating is highly
beneficial. However, despite the pharmaceutical requirements, organic film coating
has several limitations owing to the issues of flammability, the toxicity of residual
solvents and environmental safety concerns.Despite proper ventilation facilityin the
room, the complete removal of organic solvent vapours is difficult which increases
the risk of explosion and toxicity. The production costs increase due to regulatory
and environmental issues. Thus, the pharmaceutical industries are focusing more
on aqueous film coating. Aqueous film coating provides several advantages over
organic film coating in the context of environmental pollution, operation safety and
risk of explosion. The aqueous film coating initially requires upgradation in the
coating facility owing to the requirement of higher drying capacity as the latent heat
of water (2200 kJ) is much higher compared to organic solvents (e.g. methylene
chloride latent heat is 550 kJ). Thus, almost four times more energy is required
for drying in aqueous film coating compared to organic film coating [5]. Also, in
case of preparing aqueous coating solution for water-insoluble polymers, plasticizer
or a suitable suspending agent needs to be added for obtaining a homogeneous
coating solution. Nevertheless, aqueous film coating is still widely preferred in
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pharmaceutical industries as it can circumvent the safety issues that are associated
with organic film coating [6].
3 Methods for Coating Tablets
Pan coating and fluidized bed coating are the basic techniques extensively employed
for applying coating material on substrates. The chapter entails details regarding pan
coating and fluidized bed coating process along with factors affecting the process
and its optimization.
3.1 Pan Coating
The pan coating is the oldest pharmaceutical coating technique widely used since
many years for manufacturing coated tablets, pellets or granules. The key advantage
of pan coaters is that they offer relatively less mechanical stress to the core substrate
and also ascertain the desired motion of the substrate bed during the coating process.
In a conventional pan coater, the tablets are placed in a rotating pan. The coating
solution is introduced via an air atomizing spray nozzle. With the rotation of the
pan, the tablets’ top layers cascade down due to gravitational force which provides
another layer of tablets to get coated and dried before entering the tablet bed bulk.
Within defined time known as circulation time, the tablets arrive in the spray zone
which leads to repetition of coating and drying process. The process of coating in
a pan coater is represented in Fig. 2. In pan coating process the tablets movement
should occur uniformly via the spraying zone. However, sometimes the tablets enter
slow-moving or stagnant regions of the bed which leads to its reduced circulation
through the spray zone. Based on pan designs, they can be categorized as standard
coating pans (having solid walls) and perforated pans (fully or partially perforated).
While based on the kind of process, the pans can be categorized as continuous
coating pan or batch process coating pan.
(i) Standard Coating Pan
The standard coating pans also known as conventional coating pans are
widely used in pharmaceutical industries. The pan coaters can be categorized
based on their rotating axis, i.e. on an inclined axis or horizontal axis. In coater
spinning on an inclined axis, the substrate is tumbled in a conventional coating
pan which is spinning on an inclined axis. Owing to the inclination, two fundamental motions are superimposed: (a) centrifugal movement on the vertical
axis and (b) tumbling movement on the horizontal axis. The coating solution is
sprayed on the substrate through a spraying nozzle. Moreover, hot air is blown
through the coater that helps in the drying of the coat. At certain time intervals,
the substrate enters the spray zone and then cascades down and merges to the
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Fig. 2 Schematic representation of pan coating process
core bulk by which the coating and drying process keeps on repeating. However,
the inclined axis rotation leads to two disadvantages: (a) inadequate transport
of air that leads to improper drying and (b) inefficient movement of particle that
results in dead zones which in turn impairs the homogeneous mixing efficiency.
For increasing the average contact area between the drying air and the core
bed, horizontal rotating pans were developed. In the case of coater rotating on
the horizontal axis, the core bed undergoes tumbling motion that results in a
reduction of required drying time and provides increased pan volume. However,
further refinement was still required for improving the drying efficiency as well
as the particle flow. For improving the particle movement in the pan, baffles and
blades were introduced in the pan. In 1965, Keil invented single baffle coating
pan. Thereafter, Pellegrini invented horizontal axis coating pan with an integral
baffle and tapered sidewalls. The sidewalls add an additional lateral movement
that increases the particle movement efficiency. The drying air derives the
energy essential for moisture evaporation from the coating layers. Therefore,
heat and mass transfer efficiency has a significant impact on product quality.
The drying efficiency can be improved by increasing mass and heat transfer
either by rising rotation speed and temperature or by enhancing the drying air
supply. In the conventional drying method, the drying air blows only across
the core surface which leads to improper drying of the core materials. This led
to the development of different drying gadgets such as immersion sword and
immersion tube [1].
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